Disease-a-Month 60 (2014) 254262

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Disease-a-Month

journal homepage: www.elsevier.com/locate/disamonth

Angle-closure glaucoma
Krishna Patel, BS, Shuchi Patel, MD

Introduction

Glaucoma is dened as an optic neuropathy causing peripheral vision loss. The etiology of
glaucoma can be divided according to its pathophysiology. The broad classications of glaucoma
include open-angle and closed-angle glaucoma. As determined in the 2000 US census, it is
estimated that primary open-angle glaucoma affects 2.22 million US citizens. Owing to the
rapidly aging population, the number with open-angle glaucoma will increase by 50% to 3.36
million in 2020.1 In contrast, angle-closure glaucoma is not as common in the United States, as it
accounts for only 10% of all glaucoma. However, it is more prevalent worldwide with estimates
that 5.3 million people will be blinded by primary angle-closure glaucoma by 2020.2
Angle-closure glaucoma is caused by apposition of the peripheral iris to the trabecular
meshwork, resulting in reduced drainage of aqueous humor through the anterior chamber angle.
This usually occurs because the iris is either pushed or pulled anteriorly into the angle. Based on
these anatomic denitions, angle-closure glaucoma can be further classied into primary angle-
closure glaucoma or secondary angle closure. As the name indicates, primary angle closure has
no causative mechanism leading to appositional angle closure. Secondary angle closures have
identiable mechanisms for the apposition of the iris to the angle or closure of the angle by
direct blockage of the trabecular meshwork.

Primary angle-closure glaucoma

Primary angle-closure glaucoma (PACG) is caused by pupillary block in 90% of cases. Pupillary
block is caused by apposition of the iris against the lens restricting the efux of aqueous from the
posterior chamber to the anterior chamber and subsequent drainage through the trabecular
meshwork (Fig. 1). The accumulation of the aqueous in the posterior aspect causes bowing of the iris
anteriorly and eventual closure of the angle. This can happen acutely, intermittently, or chronically.
There are multiple risk factors for PACG. Patients with hyperopia, or a short axial length of the
eyeball, and an anterior chamber length of less than 2.5 mm are at an increased risk. The disease
is more common in Eskimos and Southeast Asians populations with individuals over 40 years
being at an increased risk as the lens thickens (due to cataract formation) and the anterior
chamber depth shallows. Females are at a higher risk as they tend to have shallower anterior
chambers,3 and those with a family history of PACG are also at an increased risk for the disease.

http://dx.doi.org/10.1016/j.disamonth.2014.03.005
0011-5029/ Published by Mosby, Inc.
 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262 255

Fig. 1. Pupillary block. (Woo E, Pavlin C, Slomovic A, Taback N, Buys Y. Ultrasound biomicroscopic quantitative analysis of
light-dark changes associated with pupillary block. Am J Ophthalmol. 1999;127:4347.)

Acute primary angle closure

Acute primary angle closure is caused by a sudden block of the trabecular meshwork by the
iris. Acute primary angle closure may be caused iatrogenically by mydriatics, and patients should
be evaluated for narrow angles prior to using dilating drops.
Symptoms include blurred vision, pain, colored halos around lights, nausea, emesis, and
frontal headaches. Patients with acute primary angle closure may present clinically with
increased intraocular pressure (IOP), a mid-dilated, non-reactive, or irregular pupil. On physical
exam, corneal edema may be seen in these patients secondary to the extreme sudden elevation
in pressure. Additionally, these patients may present with congested episcleral and conjunctival
vessels, shallow anterior chambers, and mild cell and are in the anterior chamber, indicative of
an inammatory process. Glaucomaecken, which are anterior subcapsular or capsular opacities
due to epithelial infarct, may be present as well. On gonioscopy, or examination of the angle, the
contralateral eye usually has narrow angles as well, and there is a 4080% chance of an acute
attack in the other eye in 510 years. A study showed that without treatment, 51.3% (58/113) of
patients developed an acute attack in the contralateral eye.4 Therefore, a prophylactic laser
peripheral iridotomy (LPI) should be performed in the fellow eye relatively soon after treatment
is started for the eye with angle closure.
The elevation in pressure should rst try to be reduced by using topical glaucoma drops, such
as beta-blockers, carbonic anhydrase inhibitors, and alpha-agonists. Parasympatheticomimetics,
such as pilocarpine, can also be used. Systemic hyperosmotic agents and topical steroids can be
used as well. If the attack is recent, corneal indention with a gonioscopy lens can break the
pupillary block and open the angle. Apraclonidine and nonselective adrenergic agonists should
be avoided, as they may cause pupillary dilation/vasoconstriction and worsen the condition.
These patients should be referred to an ophthalmologist for determination of further surgical
interventions. Denitive treatment is a LPI performed with either an argon or YAG laser,
although sometimes the procedure has to be delayed until the cornea is clear and the procedure
can be performed safely.5

Intermittent (sub-acute) angle closure

Patients with intermittent angle closure have periodic episodes of blurred vision, halos, and
mild pain. These patients often have normal IOP in between episodes, and episodes often resolve
during sleep due to miosis of the pupils. Treatment options include laser peripheral iridotomy,
cataract extraction (if present), and goniosynechiolysis.
256 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262

Chronic angle closure

Chronic angle closures occur after an episode of acute angle closure, or due to frequent
intermittent angle closures. Most occur gradually, making them difcult to diagnose. These
patients may have a lack of subjective ndings. Gonioscopy is needed to accurately diagnose
this, as chronic angle closure can be mistaken for primary open-angle glaucoma. Iridotomy is
still needed in order to remove any component of pupillary block, and these patients may still
require ocular medications or further surgery.

Narrow anterior chamber angle

A narrow anterior chamber is an anatomic nding that is a risk for angle closure. To
determine if the patient is at high risk for pupillary block, and if a prophylactic LPI is indicated,
provocative testing can be performed. There are three different tests that can be done. The
darkroom test is performed by having the patient stay in a dark room causing the pupil to dilate.
After 45 min, the pressure should be checked again. This method can identify about 50% of
patients at risk. Another test that can be done is the prone test in which the patient lies face
down for 1 h. It is more sensitive test with a sensitivity of 70%. Lastly, a phenylephrine test can be
performed. The IOP should be rechecked at 1 h after dilation or when the pupil is at least 4 mm
dilated. In any of these tests if the IOP increases by more than 8 mmHg from baseline, this is
considered a positive test and a risk factor for acute angle closure.

Plateau iris

Plateau iris the only type of primary angle closure without pupillary block. It is an anatomic
variation in which the iris root angulates forward from its insertion point, and then again
centrally6 (Fig. 2). The abnormal conguration of the anterior chamber angle may result in acute
or chronic angle-closure glaucoma. Plateau iris is most often caused by anteriorly positioned
ciliary processes that push the peripheral iris forward, which can block the trabecular
meshwork. Plateaus iris with acute angle closure is seen more commonly in young patients with
myopia (near-sightedness).

Fig. 2. Plateau iris caused anterior rotation of ciliary body. (Tran H, Liebmann J, Ritch R. Iridociliary apposition in plateau
iris syndrome persists after cataract extraction. Am J Ophthalmol. 2003;135(1):4043.)
 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262 257

In these patients, it should be noted that the central chamber depth is deeper than seen with
the patients described previously. The denitive diagnosis of plateau iris can be made if angle
closure continues to persist after iridotomy. These patients can be further treated by laser
gonioplasty and chronic treatment with miotic agents.7

Secondary angle closure with pupillary block

Lens-induced glaucoma

Phacomorphic glaucoma
Phacomorphic glaucoma is due to a large swollen lens that pushes the iris forward, leading to
an intermittent pupillary block angle closure. The initial treatment is most often with topical
medications such as beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors.8
Phacomorphic glaucoma can be treated by iridotomy for temporary relief and with cataract
extraction for denitive treatment (Fig. 3).

Microspherophakia
Microspherophakia is an abnormally shaped lens. It is often familial and can be an isolated
condition or part of other conditions such as WeillMarchesani or Marfan syndrome. The
anterior lens position and round shape lead to pupillary block angle-closure glaucoma. Medical
treatment includes cycloplegics to atten the lens and pull it more posteriorly. Conversely,
miotics worsen the condition. A LPI or lens extraction is curative.9

Ectopia lentis
Ectopia lentis occurs when there is displacement of the lens from the normal anatomic
position. It can lead to intermittent pupillary block. An ophthalmologist can treat this by creating
two laser peripheral iridotomies that are 1801 apart. Other diseases that should be kept in the
differential include pseudoexfoliation syndrome, trauma, Marfans syndrome, homocystinuria,
microspherophakia, and WeillMarchesani10 (Fig. 4).

Aphakic or pseudophakic angle-closure glaucoma

In aphakic patients without a LPI, angle closure can occur from pupillary block by the contact
between the iris and the intact anterior hyaloid face. In pseudophakic patients pupillary block
can also occur. With an anterior chamber intraocular lens (ACIOL), the lens may directly block
the pupil as it rests on the iris and therefore a peripheral iridectomy is usually made at the time

Fig. 3. Phacomorphic glaucoma. (Sowka J. Phacomorphic glaucoma. J Am Optom Assoc. 2006;77(12):586589.)

258 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262

Fig. 4. Ectopia Lentis, with upward displacement of the lens, in a patient with Marfans syndrome. (Konradsen T, Koivula
A, Kugelberg M, Zetterstro m C. Accommodation measured with optical coherence tomography in patients with Marfans
syndrome. Ophthalmology. 2009;116(7):13431348.)

of ACIOL placement. Occasionally pupillary block can occur with a posterior chamber intraocular
lens (PCIOL) due to the formation of posterior synechiae that result in iris bombe.

Vitrectomy with intraocular gas/silicone oil

Intraocular gas or silicone oil lling the posterior chamber for treatment of a retinal
detachment can also be space occupying and cause a pupillary block. Since these substances are
lighter than aqueous, an inferior LPI should be performed.

Secondary angle closure without pupillary block

Neovascular glaucoma

Neovascular glaucoma is usually caused by growth of new vessels within the angle, often due
to ocular ischemia or ocular inammation. Some causes of neovascular glaucoma include
diabetic retinopathy, ischemic retinal vessel occlusions, and ocular ischemic syndrome.11 In
cases of neovascular glaucoma, ne arborizing blood vessels can grow at the pupil margin,
extend over the surface of the iris, and also into the angle (Fig. 5). The vessels then cross the
ciliary body and scleral spur and branch over the trabecular meshwork but never onto
endothelium. A brous membrane may also grow on the trabecular meshwork, which eventually
contracts leading to peripheral anterior synechia and thus the development of secondary angle-
closure glaucoma.
Patients with neovascular glaucoma present with increased intraocular pressure and the
symptoms that are associated with that including pain, injection, corneal edema, and anterior
chamber reaction. A gonioscopy should always be performed on these patients. Overall, 10% of
the time, patients may have neovascularization within the angle without having any
neovascularization of the iris. It is important to distinguish dilated iris blood vessels due to
inammation from neovascularization.
If neovascular glaucoma is caught early and the vitreous is clear, an ophthalmologist can
perform a pan-retinal photocoagulation laser, but the effect of the laser can take weeks.
Therefore, intravitreal anti-VEGF (endothelial growth factors) medications should be considered.
If the neovascularization has regressed, but IOP remains elevated then a surgical procedure, such
as a glaucoma drainage device, may be warranted. In cases of late disease with poor visual
potential, a cyclodestructive procedure may be used.
 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262 259

Fig. 5. Neovasculization of the angle leading to glaucoma. (Iliev M, Domig D, Schnurrbursch U, Wolf S, Sarra G.
Intravitreat Bevacizumab (Avastins) in the treatment of neovascular glaucoma. Am J Ophthalmol. 2006;142(6):1054
1056.)

Iridocorneal endothelial syndrome (ICE)

There are multiple iridocorneal endothelial syndromes (ICE), including iris nevus syndrome,
Chandlers, and essential iris atropy. All of these disorders involve the corneal endothelium,
which has a beaten bronze look. The endothelium starts to behave like epithelium and
prolerates. On specular microscopy, the endothelium appears atypical with large spaces
between cells and a low cell count. An endothelial membrane can grow over the angle, iris, and
other structures. The layer of endothelial cells pulls the iris up to the cornea, leading to
peripheral anterior synechia. This results in glaucoma in about 50% of the cases. The disease is
almost always unilateral. The incidence of ICE is higher in women, and more common in people
aged 2050 years. Treatment options include hypertonic saline and glaucoma medications, but
usually it is difcult to manage medically. Glaucoma surgery may therefore be indicated and
multiple surgeries may be needed due to a higher failure rate of these procedure compared to
other conditions.12

Epithelial downgrowth

Epithelial downgrowth is a condition in which non-keratinized, stratied, squamous cell

epithelium covers corneal endothelium, trabecular meshwork, iris, and the ciliary processes
(Fig. 6). Epithelial cells can be seen in cytologic examination of the aqueous aspirate. Another
way to conrm that there are indeed epithelial cell on surfaces that they do not belong on is to
place a spot of argon laser in the area suspected to have this growth. If there are epithelial cells
there, the argon causes whitening of the tissue and helps to identify the presence of the
abnormal growth. The cells are usually present secondary to a penetrating wound or intraocular
surgery and can cause a severe secondary glaucoma by blocking the trabecular meshwork. The
treatment is by removing the epithelial membrane and affected tissues by curettage, intraocular
cryotherapy, or laser therapy. The overall prognosis of this disease is poor despite surgical
treatment of the underlying cause. Medical or surgical treatment to manage the increased
pressure is usually needed because the primary etiology is difcult to cure.

Fibrous ingrowth

Fibrous ingrowth is caused by broblast proliferation following a penetrating wound in the

anterior chamber. It is not as aggressive as epithelial downgrowth but can cause corneal
260 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262

Fig. 6. Epithelial downgrowth. (Nemi A, Bahadur R, Randleman J. Traumatic epithelial downgrowth after radial
keratotomy. J Cataract Refract Surg. 2008;34(2):327329.)

decompensation and a secondary glaucoma.13 The treatment is rst by medical therapy for the
increased pressure followed by surgical intervention if needed.

Intraocular tumors

Intraocular tumors can cause glaucoma by different mechanisms depending on the location
of the tumor. If the tumor is found in the posterior segment, the tumor may cause the irislens
diaphragm to be pushed forward, resulting in a secondary angle closure. If the tumor is in the
anterior segment, it may cause a secondary glaucoma via direct tumor invasion of the angle,
rotation of the ciliary body, intraocular heme, rubeosis iridis, deposition of tumor cells, or
inammatory or cellular debris within the trabecular meshwork. The most common type of
intraocular tumors leading to glaucoma is uveal melanoma. Treatment of the underlying cause is
usually more important than treating just the high pressure, but the pressure is managed
medically, and if needed, surgically as well.

Inammation

Inammation can cause posterior synechia and then iris bombe leading to secondary angle
closure. The peripheral anterior synechia seen secondary to inammation is often inferior and
non-uniform in shape and height. This is different than synechia that occur with primary angle
closure, in which case the peripheral anterior synechia is often superior. Treatment should be
aimed at reducing the inammation and then the pressure should be managed either medically
or surgically.

Aqueous misdirection

Aqueous misdirection, also known as malignant glaucoma, is a rare cause of glaucoma. It

almost always presents after ocular surgery, often in patients with pre-existing angle-closure
glaucoma or peripheral anterior synechia. Aqueous misdirection usually has a uniform attening
of the central and peripheral anterior chamber, and elevated intraocular pressure. Aqueous
misdirection is caused by an anterior rotation of the ciliary body with posterior misdirection of
the aqueous, combined with a block to aqueous movement into the anterior chamber. A patent
peripheral iridotomy is needed in order to make the diagnosis.
 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262 261

Medical management of aqueous misdirection should be with mydriatics, aqueous

suppressors, and hyperosmotic agents. Miotic agents should be avoided as they worsen the
condition by causing further anterior rotation of the ciliary body. YAG laser to disrupt the
anterior hyaloid face or argon laser to shrink the ciliary processes may reverse the condition.
Denitive treatment is pars plana vitrectomy.14

Retinal surgery/retinal vascular disease

A scleral buckle is one of the ways to treat a retinal detachment. The buckle encircles the eye
and pushes the sclera towards the middle of the eye to relieve the pull on the retina, placing the
retina and underlying tissue in proximity to allow the tear to heal. However, the encircling band
can cause congestive swelling with forward motion of the ciliary body and subsequent occlusion
of the angle. There can also be an increase in IOP due to obstruction to venous outow into
vortex system by the encircling band. This can be treated by cycloplegics, carbonic anhydrase
inhibitors, and topical steroids. Iridectomy is of little benet. The chamber usually deepens over
several weeks with medical therapy.

Central retinal vein occlusion

Central retinal vein occlusions (CRVO) can be a cause of glaucoma, independent of causing
neovascular glaucoma by causing early shallowing of the chamber angle, presumably due to
swelling of the choroid and ciliary body. With resolution of the CRVO, the chamber deepens.

Nanophthalmos

Nanophthalmos can be dened as a normal-shaped, but small eye. The axial length of the eye
is less than 20 mm. In this case, the lens of the eye is relatively large in comparison to the
volume of the eye. This can lead to angle closure. Also, the thickened sclera impedes vortex vein
drainage, also increasing IOP. Glaucoma in this instance can be treated by laser iridectomy, laser
iridoplasty, and medical therapy. Caution during surgical intervention needs to be taken as there
is a high risk for choroidal effusions in nanophthalmic eyes.15

Retinopathy of prematurity (ROP)/persistant fetal vasculature/persistent primary hyperplastic

vitreous (PFV/PHPV)

ROP is a disease affecting premature babies. Babies who are born before 31 weeks are at an
increased risk. Contracting retrolental tissue in ROP can cause progressive shallowing of the
anterior chamber and angle closure.
In cases of PFV/PHPV, there is a unilateral microphthalmos and elongated ciliary processes.
Glaucoma can occur due to contracture of the primary vitreous and swelling of the
cataractous lens.

Drug-induced secondary angle-closure glaucoma

Certain medications can lead to secondary angle-closure glaucoma.16 One such medication is
topiramate, which is a sulfamate-substituted monosaccharide. It can lead to an acute myopic
shift and bilateral angle-closure glaucoma due to ciliochoroidal effusion.17 Symptoms usually
begin within 1 month of initiating therapy. The rst step to treat drug-induced secondary angle-
closure glaucoma is cessation of the offending agent, followed by using aqueous suppressants
and cycloplegics. An iridotomy is not indicated for this cause of glaucoma. Interestingly enough,
acetazolamide, which is a medication used to reduce intraocular pressure, can induce this type
of secondary angle closure. Other sulfonamides, such as hydrochlorathiazide,18 can have similar
effects.
262 K. Patel, S. Patel / Disease-a-Month 60 (2014) 254262

Conclusion

In the US, POAG is more common than angle closure, yet angle closure still constitutes a large
portion of glaucoma worldwide. Despite the cause, the symptoms are usually similar due to
a signicantly increased IOP and subsequent irreversible damage to the vision. Therefore,
recognition of angle closure and the specic type is important for timely treatment to minimize
both patient discomfort and permanent visual damage.

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